Johansson Anne-Sofie, Owe-Larsson Björn, Hetta Jerker, Lundkvist Gabriella B
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Section of Psychiatry at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Schizophr Res. 2016 Jul;174(1-3):17-23. doi: 10.1016/j.schres.2016.04.029. Epub 2016 Apr 28.
Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease.
在几种精神疾病中都有昼夜节律受损的报道。精神分裂症通常与异常的睡眠-觉醒周期和失眠有关。目前尚不清楚精神分裂症是否与分子节律紊乱有关。我们分别从慢性精神分裂症患者和健康对照者的皮肤样本中培养成纤维细胞,并分析了生物钟基因CLOCK、BMAL1、PER1、PER2、CRY1、CRY2、REV-ERBα和DBP在48小时内的昼夜表达情况。在慢性精神分裂症患者的成纤维细胞中,我们发现与健康对照者的细胞相比,CRY1和PER2的节律性表达丧失。我们还评估了这些患者的睡眠质量,发现与健康对照者相比,他们中的大多数人睡眠质量较差。在另一个患者样本中,我们分析了首次发作精神病的精神分裂症患者的单核血细胞,发现与健康对照者的血细胞相比,CLOCK、PER2和CRY1的表达降低。这些新发现表明精神分裂症存在分子生物钟紊乱,对我们理解该疾病中报道的异常节律具有重要意义。